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Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells.
J Ethnopharmacol. 2021 Jun 28; 274:114081.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Chaga mushrooms (Inonotus obliquus) are commonly used in traditional treatments in Eastern Europe and Asia due to their diverse pharmacological effects, including anti-tumor and immunologic effects. Thus, many cancer patients take Chaga mushrooms as a complementary medicine, even during chemotherapy or radiotherapy. However, few studies have investigated the effects or molecular targets of Chaga mushrooms in breast cancer.

AIM OF THE STUDY

Herein, we examined the anticancer effects of Chaga mushrooms in different types of breast cancer cell lines, and explored the underlying molecular mechanism to better understand their effects and benefits.

MATERIALS AND METHODS

Chaga mushroom extract (CME) was prepared by extracting Chaga mushrooms with 70% ethanol. The cytotoxic effects of CME were assessed by MTT assay and protein expressions were evaluated by western blotting. To evaluate in vivo anti-tumor effects of CME, CME (2 g/kg) was orally administered to 4T1 tumor-bearing BALB/c mice every other day over 30 days (15 administrations), and tumor sizes were measured. Silica gel column chromatography was used to fractionate CME, and major constituents responsible for cytotoxic effects of CME were identified by 1H/13C-NMR and LC-MS.

RESULTS

CME inhibited the proliferation of 4T1 mouse breast cancer cells in a dose and time-dependent manner. The expression of LC3 and phosphorylation of AMPK were increased by CME, while the phosphorylation of mTOR, S6, and S6K1 were suppressed, suggesting that CME induced autophagy by activating AMPK and inhibiting mTOR signaling pathways. Consistent with its observed cytotoxic effect in vitro, CME effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition, inotodiol and trametenolic acid were identified as the major constituents responsible for the cytotoxic effects of CME on breast cancer cells. Moreover, inotodiol and trametenolic acid-enriched fractions both exhibited cytotoxic effects regardless of breast cancer cell subtypes and did not interfere with the cytotoxic effects of conventional drugs.

CONCLUSIONS

Taken together, Chaga mushroom extract induced autophagy by activating AMPK and inhibiting the mTOR signaling pathway. Our data suggest Chaga mushrooms may be a beneficial complementary medicine for breast cancer patients.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea.Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea.Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea.Department of Pharmacy, Woosuk University, 443 Samnye-ro, Wanju, Jeollabuk-do, 55338, Republic of Korea.Department of Pharmacy, Woosuk University, 443 Samnye-ro, Wanju, Jeollabuk-do, 55338, Republic of Korea.Department of Pharmacology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea. Electronic address: soyoungkim@dongguk.ac.kr.Department of Radiation Oncology, College of Medicine, Dongguk University, 123 Dongdae-ro, Gyeongju, Gyeongsangbuk-do, 38066, Republic of Korea. Electronic address: opencagejhs@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33798660

Citation

Lee, Min-Gu, et al. "Chaga Mushroom Extract Induces Autophagy Via the AMPK-mTOR Signaling Pathway in Breast Cancer Cells." Journal of Ethnopharmacology, vol. 274, 2021, p. 114081.
Lee MG, Kwon YS, Nam KS, et al. Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells. J Ethnopharmacol. 2021;274:114081.
Lee, M. G., Kwon, Y. S., Nam, K. S., Kim, S. Y., Hwang, I. H., Kim, S., & Jang, H. (2021). Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells. Journal of Ethnopharmacology, 274, 114081. https://doi.org/10.1016/j.jep.2021.114081
Lee MG, et al. Chaga Mushroom Extract Induces Autophagy Via the AMPK-mTOR Signaling Pathway in Breast Cancer Cells. J Ethnopharmacol. 2021 Jun 28;274:114081. PubMed PMID: 33798660.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chaga mushroom extract induces autophagy via the AMPK-mTOR signaling pathway in breast cancer cells. AU - Lee,Min-Gu, AU - Kwon,Yun-Suk, AU - Nam,Kyung-Soo, AU - Kim,Seo Yeon, AU - Hwang,In Hyun, AU - Kim,Soyoung, AU - Jang,Hyunsoo, Y1 - 2021/03/30/ PY - 2021/01/11/received PY - 2021/03/04/revised PY - 2021/03/25/accepted PY - 2021/4/3/pubmed PY - 2021/11/16/medline PY - 2021/4/2/entrez KW - AMPK KW - Autophagy KW - Breast cancer KW - Chaga mushroom KW - Inonotus obliquus KW - Inotodiol KW - Trametenolic acid KW - mTOR SP - 114081 EP - 114081 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 274 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Chaga mushrooms (Inonotus obliquus) are commonly used in traditional treatments in Eastern Europe and Asia due to their diverse pharmacological effects, including anti-tumor and immunologic effects. Thus, many cancer patients take Chaga mushrooms as a complementary medicine, even during chemotherapy or radiotherapy. However, few studies have investigated the effects or molecular targets of Chaga mushrooms in breast cancer. AIM OF THE STUDY: Herein, we examined the anticancer effects of Chaga mushrooms in different types of breast cancer cell lines, and explored the underlying molecular mechanism to better understand their effects and benefits. MATERIALS AND METHODS: Chaga mushroom extract (CME) was prepared by extracting Chaga mushrooms with 70% ethanol. The cytotoxic effects of CME were assessed by MTT assay and protein expressions were evaluated by western blotting. To evaluate in vivo anti-tumor effects of CME, CME (2 g/kg) was orally administered to 4T1 tumor-bearing BALB/c mice every other day over 30 days (15 administrations), and tumor sizes were measured. Silica gel column chromatography was used to fractionate CME, and major constituents responsible for cytotoxic effects of CME were identified by 1H/13C-NMR and LC-MS. RESULTS: CME inhibited the proliferation of 4T1 mouse breast cancer cells in a dose and time-dependent manner. The expression of LC3 and phosphorylation of AMPK were increased by CME, while the phosphorylation of mTOR, S6, and S6K1 were suppressed, suggesting that CME induced autophagy by activating AMPK and inhibiting mTOR signaling pathways. Consistent with its observed cytotoxic effect in vitro, CME effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition, inotodiol and trametenolic acid were identified as the major constituents responsible for the cytotoxic effects of CME on breast cancer cells. Moreover, inotodiol and trametenolic acid-enriched fractions both exhibited cytotoxic effects regardless of breast cancer cell subtypes and did not interfere with the cytotoxic effects of conventional drugs. CONCLUSIONS: Taken together, Chaga mushroom extract induced autophagy by activating AMPK and inhibiting the mTOR signaling pathway. Our data suggest Chaga mushrooms may be a beneficial complementary medicine for breast cancer patients. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/33798660/Chaga_mushroom_extract_induces_autophagy_via_the_AMPK_mTOR_signaling_pathway_in_breast_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(21)00308-1 DB - PRIME DP - Unbound Medicine ER -