Resin Glycosides from Ipomoea funis as Inhibitors of P‑Glycoprotein in Multidrug-Resistant Breast Carcinoma Cells

TL;DR

A new resin glycoside from a Mexican vine may help overcome drug resistance in breast cancer by enhancing chemotherapy effectiveness.

Contribution

A new resin glycoside, funisin I, was isolated and shown to enhance chemotherapy in drug-resistant breast cancer cells.

Findings

Funisin I was identified as a new resin glycoside with a unique fatty acid structure.

Intrapilosin I improved vinblastine's cytotoxicity and reversed drug resistance in MCF-7 cells.

Resin glycosides may offer new strategies to combat multidrug resistance in cancer treatment.

Abstract

Ipomoea funis Cham. & Schltdl.
is an endemic vine found in central Mexico. The use of heart-cutting
and peak-shaving methods in recycling preparative HPLC yielded funisin
I (1), an undescribed resin glycoside, along with the
known intrapilosins I (2) and V (3). Funisin
I features operculinic acid A (6) as the oligosaccharide
core. The structural similarities observed for funisin I align with
those previously reported for purginoside I (4); however,
a difference was apparent in the occurrence of dodecanoic and (−)-(2R)-methylbutyric acids as the long- and short-chain fatty
acid substituents in compound 1. Moreover, the structure
of the previously described acutacoside F (5) was corrected
by comparing its NMR data with those of 1 and 4. The three isolated glycolipids (1-3)
did not show intrinsic cytotoxicity. However, intrapilosin I (2), when combined (50 μM) with a sublethal concentration
of the antineoplastic drug vinblastine at 0.004 μM, significantly
improved its cytotoxic effect and ability to reverse the vinblastine-resistant
phenotype in MCF-7 cells by arresting the cell cycle at the G2/M phase
and acting as a competitive substrate for P-gp. Resin glycosides could
become promising alternatives for developing new therapeutic combinatory
strategies to combat multidrug resistance in cancer treatment.

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