Hispolon, A Bioactive Compound from <i>Phellinus linteus</i>, Induces Apoptosis of Human Breast Cancer Cells Through the Modulation of Oxidative Stress and Autophagy

Pangjantuk, Amorn; Chueaphromsri, Phongsakorn; Kunhorm, Phongsakorn; Phonchai, Ruchee; Chumkiew, Sirilak; Chaicharoenaudomrung, Nipha; Noisa, Parinya

doi:10.1080/22311866.2023.2191994

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Still, we do not exclude the likely involvement of additional cell-death modes, such as autophagy and ferroptosis, in MHME-induced TNBC cytotoxicity. It should be noted that previous studies have revealed that Hispolon promotes the induction of autophagy in MDA-MB-231 cells [33] and cervical cancer cell lines HeLa and SiHa [34]. Although whether MHME is pro-autophagic remains elusive, it would be interesting to clarify whether and how autophagy contributes to MHME's cytotoxic action on TNBC cells in the future.…”

Section: Discussionmentioning

confidence: 96%

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro

Liao,

Hsieh,

et al. 2023

Biomedicines

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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with few treatment options. A promising TNBC treatment approach is targeting the oncogenic signaling pathways pivotal to TNBC initiation and progression. Deregulated activation of signal transducer and activator of transcription 3 (STAT3) is fundamental to driving TNBC malignant transformation, highlighting STAT3 as a promising TNBC therapeutic target. Methoxyhispolon Methyl Ether (MHME) is an analog of Hispolon, an anti-cancer polyphenol found in the medicinal mushroom Phellinus linteus. Still, MHME’s anti-cancer effects and mechanisms remain unknown. Herein, we present the first report about MHME’s anti-TNBC effect and its action mechanism. We first revealed that MHME is proapoptotic and cytotoxic against human TNBC cell lines HS578T, MDA-MB-231, and MDA-MB-463 and displayed a more potent cytotoxicity than Hispolon’s. Mechanistically, MHME suppressed both constitutive and interleukin 6 (IL-6)-induced activation of STAT3 represented by the extent of tyrosine 705-phosphorylated STAT3 (p-STAT3). Notably, MHME-evoked apoptosis and clonogenicity impairment were abrogated in TNBC cells overexpressing a dominant-active mutant of STAT3 (STAT3-C); supporting the blockade of STAT3 activation is an integral mechanism of MHME’s cytotoxic action on TNBC cells. Moreover, MHME downregulated BCL-2 in a STAT3-dependent manner, and TNBC cells overexpressing BCL-2 were refractory to MHME-induced apoptosis, indicating that BCL-2 downregulation is responsible for MHME’s proapoptotic effect on TNBC cells. Finally, MHME suppressed SRC activation, while v-src overexpression rescued p-STAT3 levels and downregulated apoptosis in MHME-treated TNBC cells. Collectively, we conclude that MHME provokes TNBC cell apoptosis through the blockade of the SRC/STAT3/BCL-2 pro-survival axis. Our findings suggest the potential of applying MHME as a TNBC chemotherapy agent.

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Section: Discussionmentioning

confidence: 96%

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro

Liao,

Hsieh,

et al. 2023

Biomedicines

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Mushrooms and Their Compounds with Potential Anticancer Activity: A Review

Gerardo,

Maura

2024

Int J Med Mushrooms

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Mushrooms produce many metabolites that show biological activity, which can be obtained from their fruiting body, mycelium or recovered from the culture broth when mushrooms are grown in submerged fermentation. Mushrooms are a source of natural pharmaceuticals; they have been reported to have potential inhibitory or preventive activity against some diseases, including different types of cancer. Cancer represents one of the main causes of death worldwide. It is worth mentioning that despite advances in pharmacological treatments, they still present side effects in patients. In this sense, the study of the use of mushrooms in complementary treatments against cancer is of great interest. Based on studies carried out <i>in vitro</i> and, in some cases, using animal models, it has been observed that mushrooms present preventive, corrective, and therapeutic properties against different types of cancer, by stimulating the immune system, due to their antioxidant, antimutagenic, and anti-inflammatory activities, as well as the regulation of the expression of some cellular processes, cell cycle arrest, and apoptosis, etc. Based on the above, this manuscript shows a review of scientific studies that support the anticancer activity of some mushrooms and/or their bioactive compounds.

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Hispolon, A Bioactive Compound from Phellinus linteus, Induces Apoptosis of Human Breast Cancer Cells Through the Modulation of Oxidative Stress and Autophagy

Cited by 2 publications

References 26 publications

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro

Methoxyhispolon Methyl Ether, a Hispolon Analog, Thwarts the SRC/STAT3/BCL-2 Axis to Provoke Human Triple-Negative Breast Cancer Cell Apoptosis In Vitro

Mushrooms and Their Compounds with Potential Anticancer Activity: A Review

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