Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential

Yohan Seo; Sion Lee; Minuk Kim; Dongguk Kim; Sung Baek Jeong; Raju Das; Armin Sultana; SeonJu Park; Nguyen Xuan Nhiem; Phan Thi Thanh Huong; Oh-Bin Kwon; Wan Namkung; Joohan Woo

doi:10.3389/fphar.2024.1382787

Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential

Front Pharmacol. 2024 Apr 3:15:1382787. doi: 10.3389/fphar.2024.1382787. eCollection 2024.

Authors

Yohan Seo¹, Sion Lee¹, Minuk Kim², Dongguk Kim², Sung Baek Jeong¹, Raju Das³, Armin Sultana³, SeonJu Park⁴, Nguyen Xuan Nhiem⁵, Phan Thi Thanh Huong⁵, Oh-Bin Kwon¹, Wan Namkung⁶, Joohan Woo^{3

7}

Affiliations

¹ New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation (KMEDIhub), Daegu, Republic of Korea.
² Department of Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (KMEDI Hub), Daegu, Republic of Korea.
³ Department of Physiology, Dongguk University College of Medicine, Gyeongju, Republic of Korea.
⁴ Metropolitan Seoul Center, Korea Basic Science Institute (KBSI), Seoul, Republic of Korea.
⁵ Institute of Marine and Biochemistry, Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam.
⁶ College of Pharmacy, Yonsei Institute of Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea.
⁷ Channelopathy Research Center (CRC), Dongguk University College of Medicine, Goyang, Gyeonggi-do, Republic of Korea.

Abstract

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

Keywords: anoctamin 1; apoptosis; lung cancer; prostate cancer; protein reduction; vitekwangin B.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2021R1F1A1060694, NRF-2022M3A9J3073020, NRF-2022R1F1A1063364, NRF-2022K2A9A1A06088842, and RS-2023-00247033); the Vietnam Academy of Science and Technology (VAST) under grant number QTKR01.01/22-23; and the Korea Basic Science Institute (Grant no. C313000). This research was also supported by a grant from the Dongguk University Research Program of 2021 (grant number K-2021-G0002-00516).