We previously reported that Ganoderma lucidum extract (GLE) demonstrate significant anti-cancer activity against triple negative inflammatory breast cancer models. Herein, we aimed to elucidate the bioactive compounds of GLE responsible for this anti-cancer activity. We performed NMR, X-ray crystallography and analog derivatization as well as anti-cancer activity studies to elucidate and test the compounds. We report the structures of the seven most abundant GLE compounds and their selective efficacy against triple negative (TNBC) and inflammatory breast cancers (IBC) and other human cancer cell types (solid and blood malignancies) to illustrate their potential as anti-cancer agents. Three of the seven compounds (ergosterol, 5,6-dehydroergosterol and ergosterol peroxide) exhibited significant in vitro anti-cancer activities, while we report for the first time the structure elucidation of 5,6-dehydroergosterol from Ganoderma lucidum . We also show for the first time in TNBC/IBC cells that ergosterol peroxide (EP) displays anti-proliferative effects through G1 phase cell cycle arrest, apoptosis induction via caspase 3/7 activation, and PARP cleavage. EP decreased migratory and invasive effects of cancer cells while inhibiting the expression of total AKT1, AKT2, BCL-XL, Cyclin D1 and c-Myc in the tested IBC cells. Our investigation also indicates that these compounds induce reactive oxygen species, compromising cell fate. Furthermore, we generated a superior derivative, ergosterol peroxide sulfonamide, with improved potency in IBC cells and ample therapeutic index (TI > 10) compared to normal cells. The combined studies indicate that EP from Ganoderma lucidum extract is a promising molecular scaffold for further exploration as an anti-cancer agent.

Background: The obturator artery (OA) often presents multiple anatomical variations. These can be an atypical origin, variable anastomosis, or abnormal course within the pelvis. Methods: This study aimed to report a rare arterial variation in a Puerto Rican female cadaver that showed two abnormal obturator arteries with multiple pelvic branches. The OA emerged from the anterior branch of the internal iliac artery, which typically runs anteroinferior along the lateral wall of the pelvis to the upper part of the obturator foramen. Results: The atypical OA described in this report provided two variant branches. Abnormal obturator artery I (AOAI) emerged first and gave rise to three additional branches, while abnormal obturator artery II (AOAII) emerged second and gave rise to two other branches. Conclusions: Identifying these accessory arteries is essential for surgical interventions, particularly within the field of gynecology and urogynecology. Knowledge regarding anatomical variations within this region must be assessed preoperatively to decrease the risk of iatrogenic injury.