Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells

Vijayarathna, Soundararajan; Oon, Chern Ein; Chen, Yeng; Kanwar, Jagat R.; Sasidharan, Sreenivasan

doi:10.1016/j.biopha.2017.02.075

Cited by 22 publications

(17 citation statements)

References 87 publications

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“…Clerodane diterpene possessed drug resistance modifying potential against methicillin-resistant strain of Staphylococcus aureus [39]. Polyalthia longifolia methanol leaf extract has also been shown to induce apoptosis and cell cycle arrest in the HeLA cervical cell line [26]. In the current study, we examined the efficacy of MEP against PCa and determined the molecular basis of its observed effects.…”

Section: Discussionmentioning

confidence: 99%

“…It was shown that livers of extract-treated mice were protected against paracetamol-induced oxidative damage [21, 22]. Anti-inflammatory, antimicrobial, and antitumor activities of Polyalthia longifolia have also been reported [23–26]. Moreover, compounds including cycloartane, triterpenes, clerodane diterpene, tetranorditerpene, and methyl-tetranorditerpene isolated from plant leaves displayed marked growth inhibitory activity in in vitro studies against cancer cell lines [27, 28].…”

Section: Introductionmentioning

confidence: 99%

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Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies

Afolabi

Olorundare

Babatunde

et al. 2019

Oxidative Medicine and Cellular Longevity

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Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of Polyalthia longifolia (MEP) with potent activity against human leukemia cells. In the present study, we evaluated the efficacy of MEP against prostate cancer (PCa) and established the molecular basis of its effect in in vitro and in vivo models. We observed that MEP treatment resulted in a significant decrease in the growth and viability of PCa cells, associated with arrest in the G1/S phase of the cell cycle. Apoptosis was confirmed as the primary mode of MEP-induced cell death through activation of the intrinsic apoptotic machinery. Proteomic and biochemical studies identified BiP as an important target of MEP with the activation of the ER stress pathway, as a potential mechanism driving MEP-induced apoptosis. The extract exhibited strong efficacy in the PCa xenograft mouse model with significant inhibition of tumor growth and reduced tumor burden. Taken together, our findings indicate that MEP-induced apoptosis in PCa cells concomitant with the activation of the ER stress pathways results in the inhibition of tumor growth, in vitro and in vivo. Our studies provide initial evidence of the efficacy of MEP against PCa and advocate for in-depth studies in other preclinical models for its possible use in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies

Afolabi

Olorundare

Babatunde

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Bcl-2 and Bax are the most important apoptosis-inducing factors that function in the mitochondrial membrane, jointly constituting certain ion channels that regulate mitochondrial permeability transition (MPT). Once the mitochondrial membrane is subjected to damage, Bcl-2, Bax and the ratio of Bcl-2/Bax will be altered, which will trigger a series of cellular events releasing Cyt-C from mitochondria (24). In the present study, in A2780/DDP cells incubated with different concentrations of HNPG, it was demonstrated that the ROS content was notably increased, along with marked decreases in Δψm, a downregulation of Bcl-2, upregulation of Bax and decreases in the Bcl-2/Bax ratio.…”

Section: Discussionmentioning

confidence: 99%

Effects of 5‑hydroxy‑4'‑nitro‑7‑propionyloxy‑genistein on inhibiting proliferation and invasion via activating reactive oxygen species in human ovarian cancer A2780/DDP cells

2018

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Abstract. 5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG), a novel synthetic isoflavone derivative, was demonstrated to possess antitumor activity in gastric cancer and breast cancer in vitro, but its antitumor effect and mechanism in ovarian cancer has not been characterized. The aim of the present study was to investigate the effects of HNPG on inhibiting the proliferation and invasion in human ovarian cancer A2780 cell lines of cisplatin resistance (A2780/DDP) and elucidate its underlying molecular mechanism. The results indicated that HNPG presented with marked antitumor activity against A2780/DDP cells in vitro, significantly inhibited the rates of proliferation, clone formation, invasion and metastasis, and markedly induced apoptosis in dose-and time-dependent manner. Simultaneously, levels of reactive oxygen species (ROS) were increased and mitochondrial membrane potential was decreased. In addition, Bcl-2 expression was downregulated, Bax expression was upregulated, and the ratio of Bcl-2/Bax was decreased. Concurrently, levels of Cyt-C were markedly enhanced and the caspase cascade was triggered. Taken together, the results suggested that HNPG exerted anticancer effects through promoting ROS accumulation in cells, triggering mitochondrial apoptotic pathways and ultimately resulting in cells apoptosis. Therefore, HNPG serves as a potential candidate in the chemoprevention and/or treatment of cisplatin-resistant human ovarian cancer.

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“…Polyalthia longifolia belongs to the Annonaceae family and is widely distributed in India, Pakistan, and Sri Lanka which have been used as medications for thousand years 17 . Its traditional-medical indication has assessed in evidence-based approaches for decades and antibacterial, anticancer, and antiin ammatory activities have been con rmed 18 .…”

Section: Introductionmentioning

confidence: 99%

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

Chiu¹,

Shen²,

Wu³

et al. 2020

Preprint

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Background: The antitumor activity of HCD has been reported in numerous types of cancers. Moreover, the antitumor of HCD could also be applied in non-small-cell lung cancer (NSCLC) cells and further act on doxorubicin-resistant (Dox-R) of NSCLC cells. The underlying anti-cancer mechanism of HCD on Dox-R versus Dox-sensitive (Dox-S) of A549 cells was under this investigation. Methods: Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot; and further examination of its anti-cancer efficacy in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation. Result: Regardless sensitive and resistant to Dox, HCD could arrest both Dox-S and Dox-R cells at G 2 /M phase without altering the sub-G 1 cycle along with increasing cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI 3 K-ClassIII/Beclin-1 and upregulated p62/LC3-I/II expressions, further confirmed the cell autophagy after HCD-induced. Morphological observations of the mouse lung sections illustrated that fewer cancer cells accumulated around the trachea while there were less neoplastic activities found in HCD orthotopic treatment mice without liver, kidney and spleen toxicity. Conclusion: HCD exhibited the chemotherapeutic potential for lung cancer in Dox-resistant cells, suggesting natural autophagic inducer HCD provides a promising clue of new drug discovery and development for lung cancer therapy.

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Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells

Cited by 22 publications

References 87 publications

Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies

Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies

Effects of 5‑hydroxy‑4'‑nitro‑7‑propionyloxy‑genistein on inhibiting proliferation and invasion via activating reactive oxygen species in human ovarian cancer A2780/DDP cells

Diterpene 16-hydroxycleroda-3,13-dien-15,16-olide emerges non-canonical autophagic cell death in doxorubicin-resistant lung cancer

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