A study published in the journal Engineering reports that dihydrotanshinone I (DHT), a compound derived from the Chinese herb Salvia miltiorrhiza, can induce autophagic cell death in ovarian cancer cells. The research was conducted by teams from Zhejiang Chinese Medical University and Jiangsu Normal University.
Ovarian cancer is known for having one of the highest mortality rates among gynecological cancers. A characteristic of these cancer cells is their lower level of autophagic activity compared to normal cells, which may make them susceptible to therapies that further disrupt this process.
The study investigated how DHT affects ovarian cancer cells using both laboratory experiments and animal models. According to the researchers, "DHT suppressed ovarian cancer growth by targeting SORT1, a protein involved in the autophagy-lysosome pathway." Laboratory results showed that DHT promoted the formation of autophagosomes—structures involved in cellular waste disposal—while also blocking their fusion with lysosomes. This blockage led to an accumulation of autophagosomes and ultimately resulted in cell death through a process called autophagic cell death.
The effect was also observed in mice implanted with ovarian tumors. The researchers stated, "DHT treatment significantly reduced tumor growth and weight," supporting what was seen in cell culture studies. Further analysis indicated that DHT decreased levels of SORT1 protein within tumors.
The mechanism involves DHT binding directly to SORT1 and promoting its degradation via ubiquitin-dependent processes. As a result, proteins ATG5 and ATG16L1 are released, increasing autophagosome formation but disrupting their normal processing.
SORT1 is found on membranes inside cells and helps transport proteins to lysosomes. Previous research has shown that it contributes to ovarian cancer progression by promoting proliferation, migration, and invasion of cancer cells. High expression of SORT1 has been detected in over 75% of clinical ovarian tumor samples.
The authors suggest that targeting SORT1 with compounds like DHT could be a promising approach for treating ovarian cancer: "By targeting SORT1 and disrupting the autophagy-lysosome pathway, DHT induces autophagic cell death, offering a new strategy for the treatment of this deadly disease." They note that future work will focus on understanding these mechanisms further and exploring potential clinical uses for DHT.
