4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells

Satriyo, Pamungkas Bagus; Su, Chih-Ming; Ong, Jiann Ruey; Huang, Wen Chien; Fong, Iat Hang; Lin, Che‐Chern; Aryandono, Teguh; Haryana, Sofia Mubarika; Deng, Li; Huang, Chun Chih; Tzeng, Yew Min; Chao, Tsu Yi; Liu, Hui Wen; Yeh, Chi Tai

doi:10.1016/j.taap.2021.115493

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…However, GEM resistance inhibits ROS production and consequently inhibits cell death in pancreatic ductal adenocarcinoma (32). 4-AAQB triggers cell cycle arrest, apoptosis, and DNA damage by suppressing CDK2/CDK4 expression in human breast cancer and hepatocellular carcinoma cells (11,39). The present study also found that 4-AAQB upregulated cell cycle arrest and apoptosis.…”

Section: Discussionsupporting

confidence: 69%

“…Additionally, spautin-1 (an autophagy inhibitor) has been shown to increase apoptosis by inactivating the PI3K/Akt pathway in chronic myeloid leukemia cells (45). Moreover, a previous report found that cell cycle arrest and apoptosis were induced in 4-AAQB-treated MDA-MB-231 and Hs578T human breast cancer cells (11). The findings from the present study corroborate the aforementioned results and indicate that 4-AAQB induces cell cycle arrest, apoptosis, and GEM chemosensitivity by inhibiting autophagy and the PI3K/Akt signaling axis.…”

Section: Discussionmentioning

confidence: 96%

“…4-Acetylantroquinonol B (4-AAQB) is the ubiquinone derivative of Taiwanofungus camphoratus, which is identified as the major antiproliferative compound for hepatoma cells (8). In addition, 4-AAQB is known to participate in modulating many physiological and pathological processes, such as anti-inflammatory and antioxidant ability (9), amelioration of nonalcoholic steatohepatitis (9) and inhibition of osteoclast formation (10), breast cancer (11), glioblastoma (12), and hepatic cancer stem cell tumorigenicity (13).…”

Section: Introductionmentioning

confidence: 99%

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4‑Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine‑resistant pancreatic cancer cells

Chen

et al. 2022

Oncol Lett

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Gemcitabine (GEM) is a typical chemotherapeutic drug used to treat pancreatic cancer, but GEM resistance develops within weeks after chemotherapy. Hence, the development of a new strategy to overcome drug resistance is urgent. 4-Acetylantroquinonol B (4-AAQB), a ubiquinone derived from Taiwanofungus camphoratus, has hepatoprotective, anti-obesity, and antitumor activities. However, the role of 4-AAQB in enhancing GEM sensitivity is unclear. This study aimed to determine the underlying mechanisms by which 4-AAQB enhances cytotoxicity and GEM sensitivity. Cell viability was dramatically reduced by 4-AAQB (2 and 5 µM) treatment in the MiaPaCa-2 and GEM-resistant MiaPaCa-2 (MiaPaCa-2 GEMR ) human pancreatic cancer cells. 4-AAQB led to cell cycle arrest, upregulated the levels of reactive oxygen species (ROS), promoted apoptosis, and inhibited autophagy, which subsequently enhanced GEM chemosensitivity by suppressing the receptor for advanced glycation end products (RAGE)/high mobility group box 1 (HMGB1)-initiated PI3K/Akt/multidrug resistance protein 1 (MDR1) signaling pathway in both cell lines. Vascular endothelial growth factor A (VEGFA) expression, cell migration, and invasion were also inhibited by the 4-AAQB incubation. Overall, this combination treatment strategy might represent a novel approach for GEM-resistant pancreatic cancer.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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4‑Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine‑resistant pancreatic cancer cells

Chen

et al. 2022

Oncol Lett

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“…The relative abundance of different compounds in Fraction 5 obtained by comparing the signal intensity in the 1 H NMR spectrum (Figure 1) then indicated that the anti-inflammation activity might be contributed to by the presence of 4-acetylantroquinonol B (1), which is a natural ubiquinone analogue isolated from the mycelium of A. camphorata in 2009 [22]. As one of the bioactive compounds in A. camphorata, it has been reported to possess various bioactivities, which include anti-inflammatory, anti-carcinogenic, hepatoprotective, and immunomodulatory properties [22][23][24][25][26][27][28]. However, the role of 4-acetylantroquinonol B (1) in a viral-induced inflammation model has not been reported previously.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Constituents of Antrodia camphorata on RAW 264.7 Cells Induced by Polyinosinic-Polycytidylic Acid

Jiang

Lin

et al. 2022

Molecules

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Antrodia camphorata is an endemic mushroom in Taiwan. This study was designed to screen anti-inflammatory compounds from the methanolic extract of the mycelium of A. camphorata on nitric oxide (NO) production in RAW 264.7 cells induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA (dsRNA) known to be present in viral infection. A combination of bioactivity-guided isolation with an NMR-based identification led to the isolation of 4-acetylantroquinonol B (1), along with seven compounds. The structure of new compounds (4 and 5) was elucidated by spectroscopic experiments, including MS, IR, and NMR analysis. The anti-inflammatory activity of all isolated compounds was assessed at non-cytotoxic concentrations. 4-Acetylantroquinonol B (1) was the most potent compound against poly I:C-induced NO production in RAW 264.7 cells with an IC50 value of 0.57 ± 0.06 μM.

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“…These observations have been associated with advanced tumor stage and grade [105]. In NOD/SCID mice 4-AAQB treatment: ↓ tumor growth via suppressing CDK2 and CDK4 [111] female BALB/c mice ∆ Lnc712: ↓ tumor growth Via suppressing CDK2 [116] female NOD/SCID mice ALT + PD combination: ↓ tumor growth via inhibiting both cdk4 and cdk2 [117] female BALB/c nude mice Higenamine and cucurbitacin B: ↓ tumor growth via suppressing the interaction of AKT and CDK2 [120] 5-6-week old female athymic nu/nu mice CDK2/9 inhibitors, CYC065 and eribulin combination: ↓ tumor volume [124] Cervical cancer 4-week-old BALB/C nude mice ∆ hsa_circ_0000520: ↓ tumor volume and weight [128] 4-6-week-old female BALB/c nude mice ∆ circZFR: ↓ tumor growth [130] Cholangiocarcinoma 6-week old NSG mice Dinaciclib and gemcitabine combination: ↓ tumor growth [132] Colorectal cancer nude mice ↑↑ NPTX1: ↓ tumor growth via downregulating CDK2 [133] 8-10-week-old SCID mice Dual CDK2/9 inhibition: ↓ tumor growth [136] 5-week-old athymic nude BALB/c mice ∆ SLCO4A1-AS1: ↓ tumor growth [137] Gastric cancer 4-6-week-old nude BALB/c mice ∆ LINC01021: ↓ tumor volume and weight [139] Glioma 6-week-old male BALB/c mice ∆ LINC00958: ↓ tumor growth [142] male BALB/c nude mice ∆ HSP90AA1-IT1: ↓ tumor growth [143] Hepatocellular carcinoma 4-week-old female BALB/c-nu, nude mice ∆ HNRNPU: ↓ tumor volume and weight [145] 6-8-week-old male BALB/C nude mice ∆ OLA1: ↓ tumor growth and weight [148] Nude mice ↑↑ TPT1-AS1: ↓ tumor growth [149] 4-week-old athymic BALB/c mice ↑↑ miR-155: ↑ tumor weight [153] Lung cancer 6-8-week-old male immunocompetent 129S2/ SVPasCrl mice CDK2/9 inhibitor, CCT68127: ↓ tumor growth [157] BALB/c athymic nude mice PROS reduced tumor volumes and weights via inhibiting STAT3/ VEGF/ CDK2 axis [158] Medulloblastoma 6-8-week-old female Athymic Nude-Foxn1nu mice BET bromodomain inhibition and CDK2 inhibition: ↓ tumor growth [160] breast cancer, up-regulation of MTHFD2, which contributes in the cell cycle through binding to CDK2, has been associated with shorter OS, tumor grade and stage [107].…”

Section: Investigations In Clinical Samplesmentioning

confidence: 99%

A review on the role of cyclin dependent kinases in cancers

et al. 2022

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The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.

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4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells

Cited by 9 publications

References 24 publications

4‑Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine‑resistant pancreatic cancer cells

4‑Acetylantroquinonol B enhances cell death and inhibits autophagy by downregulating the PI3K/Akt/MDR1 pathway in gemcitabine‑resistant pancreatic cancer cells

Anti-Inflammatory Constituents of Antrodia camphorata on RAW 264.7 Cells Induced by Polyinosinic-Polycytidylic Acid

A review on the role of cyclin dependent kinases in cancers

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