The potential value of triterpenoids, especially pentacyclic triterpenes like betulin, betulinic acid and betulonic acid in the induction of apoptosis in malignant tumor cells has been recognized for some years now [1,2].

Betulinic acid (BetA) and betulin come from a variety of botanical sources such as the bark from Betulaceae like Betulae species, Alnus glutinosa, Corulus avellana Carpinus betulus, as well as Platanaceae like Platanus orientalis and from Rhamnaceae like Ziziphus species [3,4]. BetA and betulonic acid are thus found in many plant species, although in a low concentration compared to betulin [5]. Betulinic acid (BetA) induces apoptosis of many types of cancer cells without toxicity towards normal cells in vitro and in vivo [6].

Methods of synthesis of many derivatives of BetA and betulonic acid have been described, including amino acid, amide as well as glycosides derivatives [7,8]. Several patents on BetA analogs for the chemotherapy of cancer have been reported. Most of these patents deal with modifications at positions C-3, C-20, and C-28 [9].

In this study, we tested the anti liver carcinoma activity of two cholesteryl ester derivatives of betulinic acid in C-28: the epicholesteryl betulinate is oil-soluble and its pegylated form is water-soluble [10].

Cancer cells proliferate rapidly and require high cholesterol concentration [11].

Mullauer FB et al described that betulin, here the lesser active of the three triterpenes, is a potent anti-tumor agent that is enhanced by cholesterol [12].

Cholesterol is indeed essential for the development of the cell membrane and it is found in the lipid rafts of all our cells.

It is, therefore, an essential nutrient for the cancer cell.

The antitumor pharmacological effects consist of triggering apoptosis via the mitochondrial pathway, regulating the cell cycle and the angiogenic pathway via a variety of factors, including different transcription factors [13].

The alcoholic patient, B.H. born 06 April 1956, suffering from liver cancer developed on cirrhosis was, the 24 of Dec.2015, considered as lost for the medicine.

During hospitalization in December 2015, decompensated cirrhosis on hepatocarcinoma with the presence of ascites was diagnosed with the invasion of the portal vein.

The abdominal CT scan performed showed a 12 cm hepatocarcinoma in the right lobe.

Given the lack of therapy, the patient, Dr. in veterinary medicine, refused palliative care and decided on an experimental treatment by oral intake of two derivatives of betulinic acid. The Epicholesteryl betulinate and the Pegylated 3' α-cholesteryl betulinate.

On the Monday 28.12.15 his alpha-fetoprotein (AFP) level was at 32258 ng/ml and the D-dimers at 16658 ng/ml.

During January 2016, he took per os the cholesteryl ester BetA derivative soluble in oil described in the patent. In February, for personal reasons, he took the water-soluble form.

The patient went back to work for a year but due to persistent alcohol abuse, treatment with a single drug [14] and the now well-documented tumor heterogeneity, resistance to treatment appeared, AFP levels reincreased and the patient died in February 2017. According to his caring doctors, the positive impact of the treatment is unquestionable. No negative side effect was observed.

In the following graph, we document the observed values of AFP and D-dimers and their evolution until February 2016.

The normal physiological values for the parameters shown in the graph are as follows :

Alpha-fetoprotein - AFP : < 8 μg / L

D-Dimers : < 500 ng / ml

Neuro sensitive enolase - NSE - here not drawn : < 12 μg / L

Report of the diagonistic finding are show in figure 5