Invasiveness of endometrial cancer cell lines is potentiated by estradiol and blocked by a traditional medicine Guizhi Fuling at clinically relevant doses

Sidra Khan; Alanah Varricchio; Carmela Ricciardelli; Andrea J Yool

doi:10.3389/fonc.2022.1015708

Invasiveness of endometrial cancer cell lines is potentiated by estradiol and blocked by a traditional medicine Guizhi Fuling at clinically relevant doses

Front Oncol. 2023 Jan 16:12:1015708. doi: 10.3389/fonc.2022.1015708. eCollection 2022.

Authors

Sidra Khan¹, Alanah Varricchio¹, Carmela Ricciardelli², Andrea J Yool¹

Affiliations

¹ School of Biomedicine, University of Adelaide, Adelaide, SA, Australia.
² Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.

Abstract

The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Results here are the first to demonstrate dose-dependent inhibition of cell motility by Fuling in two endometrial cancer cell lines, classified as Grade I which is responsive to progesterone treatment, and Grade III (MFE-280) which is resistant. The major outcome of this study was the novel demonstration that Fuling (30-80 µg/ml) significantly inhibits invasiveness in both high and low grades of EC cells, achieving 70-80% block of trans-barrier migration without cytotoxicity. This effective dose range is estimated to be comparable to that used in human clinical trials and traditional practice. Results here further show that clinically relevant doses of Fuling override the motility-promoting effects of estradiol in endometrial cancer cell lines. Medroxyprogesterone acetate has to date been the standard therapy to treat metastatic or inoperable endometrial cancers; however, success rates are low with high rates of recurrence, due in part to acquired resistance to medroxyprogesterone acetate therapy. The discovery here that Fuling appears to control the spread of treatment-resistant advanced cancers is an exciting prospect.

Keywords: cell invasiveness; endometrial cancer; estradiol; guizhi fuling; phytomedicine; progestin; women’s reproductive health.

Grants and funding

This research was funded by the Australian Research Council (grant number 19ARC_DP190101745) to AY; and The University of Adelaide Research Training Scholarships to SK and AV.